Henning Morawietz

Endothelium and cardiovascular diseases

Previous and current research

Cardiovascular diseases are the major cause of mortality in the industrial countries. Arteriosclerosis is considered to play a key role in this process, because the progression of this disease increases the risk of hypertension, coronary heart disease, heart attack and stroke. The endothelial cells form the inner layer of the blood vessels and play an important in the development and progression of arteriosclerosis.

Local differences in hemodynamic forces acting by the flowing blood on the cells of the vessel wall have been postulated as a putative mechanism for the localization of arteriosclerotic plaques. One major focus of our research is therefore the identification of molecular changes in response to different hemodynamic forces in human endothelial cells. A second research focus is the investigation of putative proarteriosclerotic mechanisms like increased NAD(P)H oxidase-dependent oxidative stress or augmented uptake of oxidized low-density lipoprotein in response to the vasoactive peptides endothelin-1 and angiotensin II in endothelial cells. In addition, we are interested in the mechanisms of the arteriovenous differentiation of endothelial cells and the formation of new blood vessels.

Occlusion of femoral artery		Development of vascular   networks from endothelial cells

We extend our in vitro studies in experimental and clinical studies in vivo and analyze the putative antiarteriosclerotic potential of pharmacological intervention in the renin-angiotensin system or lipid-lowering drugs.

Future prospects and goals

Endothelial cells play a major role in the development and differentiation of the vascular system. The development of a functional vascular system is also a crucial step in survival of regenerating tissue. Risk factors like oxidative stress and low-density lipoproteins can accelerate endothelial dysfunction and arteriosclerosis. In further studies, we will try to understand the molecular mechanisms underlying these processes and develop therapeutic strategies in the treatment of cardiovascular diseases. Using techniques of molecular and cell biology, transgenic models and clinical studies we will try to answer the following questions:

1.      What is the role of endothelial dysfunction in the development of vascular diseases?

2.      Is the increased formation of reactive oxygen species and oxidized lipoproteins involved in these processes?

3.      How differentiate endothelial cells into an arterial or venous phenotype?

4.      What are the molecular mechanisms of the formation of new blood vessels?

About

1990: PhD, University of Halle, Germany 1990-1994: Postdoctoral fellow, Institute of Genetics, University of Halle, Germany, Studies at Universities of Cologne (1991) and Geneva (1993) 1994-1995: Group Leader, Institute of Pathophysiology, University of Halle, Germany 1995-1996: Postdoctoral Fellow, Cardiovascular Research Institute, University of California, San Francisco, California 1996-2002: Group Leader, Institute of Pathophysiology, University of Halle, Germany 2002-2003: Assistant Professor, Institute of Pathophysiology, University of Halle, Germany since May 2003 Full Professor and Head of Dept. of Vascular Endothelium and Microcirculation, Medical Clinic and Policlinic III, TU Dresden

Selected publications

U. Rueckschloss, J. Galle, J. Holtz, H.-R. Zerkowski, H. Morawietz (2001): Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of HMG-CoA reductase inhibitor therapy. Circulation, 104, 1767-1772.

P. Ellinghaus, R.J. Scheubel, D. Dobrev, U. Ravens, J. Holtz, J. Huetter, U. Nielsch, H. Morawietz (2005): Comparing the global mRNA expression profile of human atrial and ventricular myocardium with high-density oligonucleotide arrays. J. Thorac. Cardiovasc. Surg., 129, 1383-1390.

H. Morawietz, S. Erbs, J. Holtz, A. Schubert, M. Krekler, W. Goettsch, O. Kuss, V. Adams, K. Lenk, F.-W. Mohr, G. Schuler, R. Hambrecht (2006): Endothelial protection, AT1 blockade and cholesterol-dependent oxidative stress: The EPAS trial. Circulation, 114, I-296-301.

W. Goettsch, C. Gryczka, T. Korff, E. Ernst, C. Goettsch, J. Seebach, H.-J. Schnittler, H. G. Augustin, H. Morawietz (2008): Flow-dependent regulation of angiopoietin-2. J. Cell. Physiol., 214, 491-503.

B. Eichhorn, G. Muller, A. Leuner, T. Sawamura, U. Ravens, H. Morawietz (2009): Impaired vascular function in small resistance arteries of LOX-1 overexpressing mice on high-fat diet. Cardiovasc. Res., 82, 493-502.
 

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